Abstract
BackgroundIt is presently unclear whether glycemic variability (GV) is associated with baroreflex sensitivity (BRS), which is an early indicator of cardiovascular autonomic neuropathy. The present study is the first to examine the relationships between BRS and GV measured using continuous glucose monitoring (CGM).MethodsThis was a multicenter, prospective, open-label clinical trial. A total of 102 patients with type 2 diabetes were consecutively recruited for this study. GV was assessed by measuring the standard deviation (SD), glucose coefficient of variation (CV), and the mean amplitude of glycemic excursions (MAGE) during CGM. The BRS was analyzed from electrocardiogram and blood pressure recordings using the sequence method on the first day of hospitalization.ResultsA total of 94 patients (mean diabetes duration 9.7 ± 9.6 years, mean HbA1c 61.0 ± 16.8 mmol/mol [7.7 ± 1.5%]) were analyzed. In the univariate analysis, CGM-SD (r = − 0.375, p = 0.000), CGM-CV (r = − 0.386, p = 0.000), and MAGE (r = − 0.395, p = 0.000) were inversely related to BRS. In addition to GV, the level of BRS correlated with the coefficient of variation in the R–R intervals (CVR-R) (r = 0.520, p = 0.000), heart rate (HR) (r = − 0.310, p = 0.002), cardio-ankle vascular index (CAVI) (r = − 0.326, p = 0.001), age (r = − 0.519, p = 0.000), and estimated glomerular filtration rate (eGFR) (r = 0.276, p = 0.007). Multiple regression analysis showed that CGM-CV and MAGE were significantly related to a decrease in BRS. These findings remained after adjusting the BRS for age, sex, hypertension, dyslipidemia, HR, eGFR, CAVI, and CGM-mean glucose. Additionally, BRS was divided according to quartiles of the duration of diabetes (Q1–4). BRS decreased after a 2-year duration of diabetes independently of age and sex.ConclusionsGV was inversely related to BRS independently of blood glucose levels in type 2 diabetic patients. Measurement of BRS may have the potential to predict CV events in consideration of GV.Trial registration UMIN Clinical Trials Registry UMIN000025964, 28/02/2017
Highlights
It is presently unclear whether glycemic variability (GV) is associated with baroreflex sensitivity (BRS), which is an early indicator of cardiovascular autonomic neuropathy
Multivariate analysis of BRS Multiple regression analysis showed that continuous glucose monitoring (CGM)-coefficient of variation (CV) and mean amplitude of glycemic excursions (MAGE) were inversely related to BRS
Results showed that CGM-standard deviation (SD), CGM-CV, and MAGE were inversely related to BRS
Summary
It is presently unclear whether glycemic variability (GV) is associated with baroreflex sensitivity (BRS), which is an early indicator of cardiovascular autonomic neuropathy. The present study is the first to examine the relationships between BRS and GV measured using continuous glucose monitoring (CGM). Baroreflex sensitivity (BRS), which is a sensitive measure of cardiovascular autonomic neuropathy (CAN) in type 2 diabetic patients [1, 2], is associated with cardiovascular disease events [3,4,5]. Risk factors involved in the reduced BRS in type 2 diabetes have yet to be fully elucidated. Reported risk factors for reduced BRS include hyperglycemia, diabetic duration, older age, obesity, hypoadiponectinemia, arteriosclerosis, and hypertension [6,7,8,9,10,11,12]. The recent clinical application of continuous glucose monitoring (CGM) and flash glucose monitoring has allowed detailed assessment of GV [20]
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